MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 PRESENTED WITH MANIC-DEPRESSIVE DISORDER - A CASE-REPORT WITH AN IDENTIFIED MEN1 GENE MUTATION

We report a case of multiple endocrine neoplasia type 1 who had repeat ed hypoglycemic episodes and had previously been diagnosed with bipola r manic-depressive disorder. The patient had a positive family history of multiple endocrine neoplasia type 1 and had multiple pancreatic en docrine tumors, hyperparathyroidism and possibly a pituitary tumor. Th e pancreatic tumors were resected by subtotal pancreatectomy and exami ned by histochemical staining and gene analysis. The tumor cells were positive for immunoreactive insulin and glucagon. A microsatellite pol ymorphism analysis revealed loss of heterozygosity on 11q13 in the tum ors. By polymerase chain reaction-based nucleotide sequencing, we iden tified a germline mutation 483del2 of the MEN1 gene in the normal panc reatic tissue of the patient. This mutation causes a shift of the read ing frame of menin mRNA at codon 125. It seems that the wild type alle le of the MEN1 gene had been lost in the tumor cells whereas the mutan t allele remained intact. This is the first identified MEN1 gene mutat ion in Japanese families and is different from all MEN1 gene mutations reported previously.